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Cell cycle-controlled interaction of nucleolin with the retinoblastoma protein and cancerous cell transformation

Item Type:Article
Title:Cell cycle-controlled interaction of nucleolin with the retinoblastoma protein and cancerous cell transformation
Creators Name:Grinstein, E. and Shan, Y. and Karawajew, L. and Snijders, P.J. and Meijer, C.J. and Royer, H.D. and Wernet, P.
Abstract:Retinoblastoma protein (Rb) is a multifunctional tumor suppressor, frequently inactivated in certain types of human cancer. Nucleolin is an abundant multifunctional phosphoprotein of proliferating and cancerous cells, recently identified as cell cycle-regulated transcription activator, controlling expression of human papillomavirus type 18 (HPV18) oncogenes in cervical cancer. Here we find that nucleolin is associated with Rb in intact cells in the G1 phase of the cell cycle, and the complex formation is mediated by the growth-inhibitory domain of Rb. Association with Rb inhibits the DNA binding function of nucleolin and in consequence the interaction of nucleolin with the HPV18 enhancer, resulting in Rb-mediated repression of the HPV18 oncogenes. The intracellular distribution of nucleolin in epithelial cells is Rb-dependent, and an altered nucleolin localization in human cancerous tissues results from a loss of Rb. Our findings suggest that deregulated nucleolin activity due to a loss of Rb contributes to tumor development in malignant diseases, thus providing further insights into the molecular network for the Rb-mediated tumor suppression.
Keywords:Cell Cycle, Human papillomavirus 18, Neoplasms, Neoplastic Cell Transformation, Neoplastic Gene Expression Regulation, Phosphoproteins, Protein Binding, RNA-Binding Proteins, Retinoblastoma Protein, Tumor Cell Line, Tumor Suppressor Proteins
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:281
Number:31
Page Range:22223-22235
Date:4 August 2006
Official Publication:https://doi.org/10.1074/jbc.M513335200
PubMed:View item in PubMed

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